Yiqing Wang

Female reproductive tract infections (RTIs) are a major health challenge worldwide and are the leading cause of infertility and adverse pregnancy outcomes. The rising incidence of RTIs highlights their status as a major public health issue. Microbial dysbiosis, particularly bacterial, fungal, and viral infections, constitutes the primary etiological factor disrupting female reproductive health. Antimicrobial peptides (AMPs) are evolutionarily conserved host defense molecules that exhibit broad‐spectrum antimicrobial activity against pathogens, as well as anti‐inflammatory and immunomodulatory properties. This review systematically summarizes the structural diversity, biological sources, and mechanistic pathways of human‐derived AMPs in combating RTIs, with a particular emphasis on their therapeutic potential in fertility preservation. Emerging evidence suggests AMPs as promising alternatives to conventional antibiotics in the post‐antibiotic era.

Endometrial cancer (EC) is a prevalent gynecological cancer worldwide, often associated with poor prognosis after recurrence or metastasis. Oroxylin A (OA) is an active flavonoid compound with a strong anti-tumor function. However, the effects of OA on EC remain unknown. In this study, we planned to investigate the anti-EC effects of OA and explore its mechanisms. Five cell lines were used for in vitro experiments, and female BALB/c nude mice were applied for xenograft experiments. The cytotoxicity and experimental concentration of OA were detected by CCK-8. Wound healing, transwell, and colony formation assays were used to evaluate the anti-metastatic and anti-proliferative activities of OA on EC cells. TUNEL assay and flow cytometry were applied for the evaluation of apoptosis. Network pharmacology was used to explore potential targets, and molecular dynamics simulations and dockings were applied for the quantification of binding energy, and stability of OA. RT-qPCR, WB, and immunofluorescence were applied for the detection of localization and expression of correlated markers. The results showed that OA notably inhibited the proliferation, migration, and invasion of Ishikawa cells. Meanwhile, in vivo Ishikawa xenograft assays demonstrated that OA notably inhibited growth and promoted apoptosis of EC. Mechanistically, after treatment with OA, the expressions of Cleaved Caspase-3, BAX, E-cadherin, and ERβ were increased, while the expressions of Bcl-2, Vimentin, N-cadherin, MMP2, MMP9, PI3K and phospho-AKT (Ser473) were decreased. Therefore, OA may exhibit significant anti-EC effects by regulating the ERβ/PI3K/AKT pathway to promote apoptosis and inhibit epithelial-mesenchymal transition (EMT).

The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial–mesenchymal transition in IUA models.

Intrauterine adhesion (IUA) is a common gynecological disease with limited therapeutic options. Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog with some anti-fibrotic and anti-inflammatory properties; however, its action on IUA remains uncertain. The purpose of the experiments in this study was to explore the effect of dulaglutide on IUA and to elucidate its mechanism to provide new ideas for the clinical treatment of IUA. An IUA mouse model was established via mechanical curettage and inflammation induction; mice received subcutaneous injection with three doses of dulaglutide once a day for two weeks (treatment) or equal amounts of sterile ddH₂O (control), and sham-operated mice were treated similarly to the control mice. Mice were sacrificed, and uterine tissues were subjected to hematoxylin and eosin (H&E) and Masson’s trichrome staining for histomorphological and pathological analyses and real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) for gene and protein expression analyses. Dulaglutide improved the shape of the uterine cavity, increased endometrial thickness and the number of glands, and significantly reduced the area of collagen fiber deposition in the endometrium. It significantly reduced collagen type I A 1 (COL1A1), interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-C motif chemokine ligand 2 (CCL2), F4/80 (macrophage), vimentin and transforming growth factor-beta (TGF-β) mRNA levels and COL1A1, IL-1β, IL-6, TNF-α, F4/80, vimentin, E-cadherin, TGF-β, and p-Smad2 protein expression levels. This study demonstrates that dulaglutide reduces inflammatory responses by inhibiting M1 macrophage polarization and inflammatory factor release and may ameliorate fibrosis by inhibiting epithelial–mesenchymal transition (EMT) via TGF-β/Smad2 signaling.

The molecular mechanisms underlying unexplained recurrent implantation failure (RIF) remain unclear. This study aimed at identifying potential biomarkers, exploring relevant signaling pathways, and analyzing the contribution of immune cell infiltration in RIF. Microarray expression datasets were extracted from the Gene Expression Omnibus database to perform bioinformatic analyses. The results showed that ten hub genes may predict RIF with high specificity and sensitivity (area under the curve = 1.000). Protein–protein interaction analysis revealed close interactions between the hub genes and the endometrial receptivity array. The real-time quantitative polymerase chain reaction further validated three potential biomarkers (RAB32, TRIB2, and FAM155B). Functional enrichment analyses indicated that immune pathways were significantly downregulated and lipid metabolism pathways were significantly upregulated in RIF compared with the controls. Significant negative correlations were observed between fatty acid biosynthesis and the immune pathways. Immune cell infiltration, including those in CD56dim natural killer, dendritic, Th1, Th2, and regulatory T cells, as well as macrophages, was significantly reduced in RIF compared with the controls used herein. This study may provide a novel perspective on the diagnosis and treatment of RIF.

Owing to its difficulty in degrading and ease of accumulation in the body, perfluorooctanoic acid (PFOA) has a detrimental effect on reproduction. This study aimed to examine the effect of PFOA concentration in follicular fluid during ovulation stimulation on embryo quality and the impact of PFOA exposure on the metabolic components of follicular fluid. This was a single-center prospective study that included 25 patients with diminished ovarian reserve (DOR), 25 with normal ovarian reserve (NOR), and 25 with polycystic ovary syndrome (PCOS). Follicular fluid samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. We demonstrated that the PFOA levels of follicular fluid in the DOR group were higher than those in the NOR group and PCOS group (P < 0.05). PFOA concentration in the PCOS group was negatively correlated with high-quality embryos (P < 0.05). To gain more insight into the impact of PFOA on the metabolic composition of follicular fluid, we classified the DOR group based on the PFOA concentration, for which metabolomic analysis was performed. In the high-concentration PFOA group, there was an increase and a decrease in three and nine metabolites, respectively, compared to that in the low-concentration group. These results suggest that PFOA may alter the metabolic composition of follicular fluid, thus, affecting ovarian reserve function.